Late Fatal Infections Remain Higher Than Expected in Adults Receiving Allogeneic Stem Cell Transplant

Introduction:

Life expectancy remains lower than expected in long-term survivors after allogeneic stem cell transplant (HCT) compared to the age and sex matched population. Infection has been reported to account for 10-20% of deaths occurring 2 years or later after HCT. We performed an analysis of late fatal infections (LFI) in HCT recipients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR).

Methods:

Adult patients (pts) who underwent first HCT between 01/1995 and 12/2011, reported to the CIBMTR and surviving disease-free at 2 years following HCT were included in the analysis. Pts transplanted at centers with follow up completeness index < 80% at 4 years post HCT were excluded. Late fatal infections were described and their cumulative incidence was calculated as death from infectious complications occurring at least 2 years after HCT in eligible subjects. Risk factors for LFI were identified using Cox regression models. Pts with late relapse or second HCT (after 2 years) were censored at the event.

Results:

There were 10,336 pts from 267 centers included in the analysis. The median age at transplant was 44 (18-79) years. Myeloablative and reduced intensity/non-myeloablative conditioning was given to 6,807 (66%) and 3,339 (32%) pts respectively. Bone marrow, peripheral blood and cord blood were used as the graft source in 3,479 (34%), 6,347 (61%) and 510 (5%) pts respectively. Clinically significant fungal infections prior to HCT, were reported in 884 (9%) pts and 318 pts (3%) were HIV positive. A history of acute GVHD (aGVHD), limited or extensive cGVHD within 2 years of HCT was reported in 3,559 (34%), 1,315 (13%) and 4,912 (48%) pts respectively. Overall 2245 pts (22%) died from any cause.

Infection, as the primary or a contributing cause of death, was reported in 687 (7%) subjects, thus LFI contributed to 31% of all late deaths. Bacterial infections were the most commonly reported LFI (Table1). The cumulative incidence of LFI in pts increased with time, with estimates of 2%, 3%, 5%, 5% and 6% at 3, 5, 8, 10 and 12 years respectively.

In multivariate analysis, increasing age >20 years, receipt of MUD or MMUD, history of aGVHD or extensive cGVHD within 2 years of HCT, male sex, and TBI-based conditioning regimens were associated with increased risk of LFI (Table 2).

Conclusions:

LFI in HCT recipients remain high and contributed to third of all deaths occurring at least 2 years after HCT. Age, HLA match, male gender, and a history of both aGVHD and cGVHD were associated with an increased risk of LFI. Risks of LFI do not diminish but increase up to 12 years of follow up.

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